TURQUOISE-II: Three-drug regimen yields high SVR in genotype 1 cirrhotic patients
LONDON — Multitargeted therapy of ABT-450 with ritonavir, ombitasvir and dasabuvir yielded strong response rates with few discontinuations among patients with cirrhosis and hepatitis C genotype 1 treated for 12 or 24 weeks, according to findings presented here.
HCV Next Editorial Board member Fred Poordad, MD, of The Texas Liver Institute and University of Texas Health Science Center in San Antonio, presented findings on the NS3/4A protease inhibitor ABT-450 with ritonavir 100 mg (ABT-450/r), the NS5A inhibitor ombitasvir (formerly ABT-267) and NS5B RNA polymerase inhibitor dasabuvir (formerly ABT-333; all three drugs from AbbVie).
Eligible participants all had genotype 1 disease, were treatment-experienced and had compensated cirrhosis.
“Cirrhosis remains a difficult-to-treat population, even in the direct-acting antiviral era,” Poordad said. “TURQUOISE-II is the first phase 3 study exclusively in cirrhotic genotype 1 patients.”
Serum albumin ≥2.8g/dL, total bilirubin <3 mg/dL, serum alpha-fetoprotein ≤100 ng/mL, international normalized ratio (INR) ≤2.3 and platelet count ≥60,000 cells/mL were some of the key eligibility criteria, according to the results.
The analysis included 208 patients who were assigned to the three-drug regimen plus ribavirin for 12 weeks and 172 patients who were treated with the same regimen for 24 weeks. Patient demographics were matched between the two arms, and all patients were followed for 48 weeks. Sustained virologic response at 12 weeks (SVR12) served as the primary outcome measure. The noninferiority threshold for this endpoint was 43%, and the superiority threshold was 54%, according to Poordad.
The primary endpoint of SVR12 was reached by 91.8% of patients in the 12-week arm and 95.9% of patients in the 24-week arm. “Our results showed no statistical difference between the 12- and 24-week arms,” Poordad said during his presentation.
Patients with genotype 1a disease who were treated for 12 weeks achieved an SVR12 rate of 88.6%. Genotype 1a patients treated for 24 weeks reached an SVR12 rate of 94%. “For genotype 1b disease, almost everyone achieved SVR,” Poordad said. “The rate was almost 100% except for a prior partial responder. “When measured by surrogates of portal hypertension and hepatic function, high SVR rates were achieved with no appreciable difference between either arm.”
The lowest SVR12 rates were reported in prior null responders in the 12-week arm, at 80%, which drove most of the difference in relapse between the two arms.
“Ribavirin dose modification occurred in only 11% of the cohort,” Poordad said. “All of these patients went on to achieve SVR.”
Age, sex, ethnicity and BMI at baseline did not predict failure, and biologic breakthrough was an unusual event in either arm. Most of the patients who relapsed were prior null responders, according to Poordad.
Virologic failure occurred in 17 patients. Of those, 15 had at least one resistance-associated variant.
Adverse event rates were similar in both arms. Patients in the 24-week arm experience slightly more fatigue and dyspnea.
“Any adverse events were common in both arms, but most were mild to moderate,” Poordad said. “Overall, around 2% overall had adverse events that led to discontinuation. Hepatic decompensation events were rare in this study, occurring in 4 patients (<1%), none of which were related to study drug.””
For more information:
Poordad F. N Engl J Med. 2014;doi:10.1056/NEJMoa1402869.
Disclosure: This study was supported by AbbVie. Poordad reports serving as a consultant/adviser for AbbVie.